1. Field of the Invention
The present invention relates to an analytical instrument for mass analysis and a method using the same.
2. Description of the Related Art
A mass spectrometer is generally used for quantitative measurement, and a method described in “Xu X et al., Rapid Communications in Mass Spectrometry, 17,832, 2003” (hereinafter referred to as “Non-patent Document 1”) is best known as a method for quantitative determination. In this method, a standard sample (or a target compound) of known concentration is previously introduced into the mass spectrometer to obtain the correlation (also termed a calibration curve) between concentration and signal intensity. Then, in this method, a target sample is introduced to determine its concentration. However, there is an inherent problem in the mass spectrometer. That is, when ionization takes place, the accuracy of quantitative determination is seriously affected because the signal intensity (or sensitivity) for the sample concentration varies greatly, depending on the influence of impurity components present in the sample (this phenomenon is termed matrix effects), or depending on the day-to-day conditions of the mass spectrometer.
A quantitative determination method given below is used in order to solve this problem.
U.S. Pat. No. 6,580,067 (hereinafter referred to as “Patent Document 1”) discloses a method including the process of adding, as an internal standard, a different similar compound. It is considered to be preferable to add, to a target sample, a compound having a chemical property similar to that of the target sample, and also forming ions having a different m/z value from that of the target sample. As a suitable material to be added, used is a material resulting from replacement of at least one element (e.g., carbon or hydrogen) of a target compound by an isotope thereof. In this instance, sensitivity changes in the addition compound are assumed to be substantially the same as sensitivity changes in the target compound, thereby making it possible to calibrate the sensitivity changes caused by the matrix effects or the conditions of the mass spectrometer.
Described in “Ito S et al., J. Chromatography A 943, 39, 2001” (hereinafter referred to as “Non-patent Document 2”) is a method including two measurements, which are made on a target sample with a target compound itself of known concentration added thereto, and on a target sample without the target compound added thereto (namely, standard addition method). This method enables calibrating the sensitivity changes caused by the matrix effects or the conditions of the mass spectrometer, because this method is capable of estimating the sensitivity of the target compound from a difference between the signal intensity of a target internal standard sample and the signal intensity of an added sample.
“Bonfiglio R et al., Rapid Communications in Mass Spectrometry, 13(12), 1175, 1999” (hereinafter referred to as “Non-patent Document 3”) gives a description as to a validation method for judging whether or not there is a necessity to calibrate the sensitivity changes caused by the matrix effects or the conditions of the mass spectrometer. Although the methods described in Patent Document 1 and Non-patent Document 2 are effective approaches for calibrating the sensitivity changes caused by the matrix effects or the conditions of the mass spectrometer, the methods lead to a rise in a total cost of measurement, because the methods requires its stable isotope and needs a complicated measurement means for adding a known quantity of a target compound. Thus, generally used is a method that includes the process of: making a separation between matrix components and the target compound, using a pretreatment means such as solid phase extraction or liquid chromatography, prior to the introduction of the target compound into the mass spectrometer; and then introducing the target compound into the mass spectrometer. Incidentally, this method includes the process of: introducing a known quantity of similar compound into the pretreated components; and then monitoring the sensitivity. Here, this method is used to ensure that the separation is sufficient for the sensitivity to be equivalent to the sensitivity observed at the time of formation of the calibration curve. If the sensitivity of an addition compound is affected by the matrix components, a pretreatment process can be repeatedly improved for eventual development of a pretreatment measurement method such as does not affect the sensitivity. This method eliminates the need to add a reference standard for each target component, because of using the previously generated calibration curve for quantitative determination.